Abstract: The invention provides novel phosphoantigen salts and novel crystalline phases of phosphoantigens salts, that the latter including non-solvated polymorphs, and solvates useful as pharmaceuticals. The invention also provides pharmaceutical compositions comprising, and processes for making, novel phosphoantigen crystalline phases. Methods of using such compositions for the treatment of disease, immunostimulatory or immune response modifying use are also provided. The invention also provides method for obtaining phosphoantigen crystals as well as highly pure phosphoantigen compositions.

Abstract: The present invention is directed to a compound of formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof, and methods for treating inflammatory and serine protease mediated disorders.

Abstract: This invention provides methods, novel formulations and kits to reduce the toxicity of anticancer drugs. Disclosed are therapeutics and treatment methods employing anticancer drags that exhibit a known toxicity, including, for example, adriamycin, campthothecin, and the like, chemically linked to a phosphonoformic acid partial ester resulting in a novel formulation that significantly decreases drug-related toxicity, enhances synergy with other chemotherapeutic drugs and provides increased efficacy against drug-resistant cancers.

Abstract: The invention is directed to TRPM8 antagonists of Formula (I). More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating TRPM8-mediated disorders. Pharmaceutical and veterinary compositions and methods of treating pain and various other disease states or conditions using compounds of the invention are also described.

Abstract: Ac-Phe-Tyr-phosphoSer-?[CH?C]-Pro-Arg-NH2AND Fmoc-bis(pivaloylmethoxy)phosphoSer-?[CH?C]-Pro-2-aminoethyl-(3-indole); and their Phospho-(D)-serine stereoisomers are novel compounds. ? refers to a pseudo amide. Such novel compounds advantageously may be used as alkene mimics.

Abstract: The present invention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: The invention provides a novel class of xanthene dyes, some of which are functionalized to allow their coupling to conjugation partners of interest, e.g. biomolecules, drugs, toxins and the like. Also provided are conjugates of the dyes, methods of preparing and using the dyes and their conjugates and kits including the dyes and their conjugates.

Abstract: The present intention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: Compounds are provided having the following structure and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, U, V, W, Y, and n are as defined above, which compounds are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids, for example, lowering LDL cholesterol and/or increasing HDL cholesterol, and treating hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis as well as Alzheimer's disease and osteoporosis and may be employed as hormone replacement therapy. A method for treating the above diseases employing the above compounds is also provided.

Abstract: Reagents are provided for the introduction of phosphonate groups into fluorescent dyes. Methods are also provided for preparing dye conjugates.

Abstract: The present invention features compounds that are HIV integrase inhibitors and may be useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

Abstract: The present invention provides a novel process for preparation of bisphosphonic acids or salts thereof, e.g. alendronic acid, by reacting a carboxylic acid, phosphorous acid and a halophosphorous compound in a water miscible neutral solvent.

Abstract: The present invention is to relate an improved process using anisole as solvent for the preparation of compound of formula (I) and its pharmaceutically acceptable salts thereof. wherein R represents —NR1R2, or a group n=1, 2, 3, 4 and 5, where R1 and R2 may be same or different and independently represents hydrogen, or C1-6 alkyl.

Abstract: Bisphosphonate compounds and related methods of making and using are disclosed, including pyridinium-1-yl, quinolinium-1-yl, and related compounds. The activity of compounds is disclosed in the context of functional assays such as Leishmania major farnesyl diphosphate synthase (FPPS) inhibition, Dictyostelium discoideum growth inhibition, human gamma delta T cell activation, and bone resorption. The applicability of bisphosphonate compounds in the context of parasitic infections, for example against trypanosomes, is disclosed. Further potential applications of the invention are disclosed regarding the treatment of one or more conditions such as bone resorption disorders, cancer, bone pain, infectious diseases, and in immunotherapy.

Abstract: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue.

Abstract: Selective phosphorylation of phenpanstatin (3a) with tetrabutylammonium dihydrogen phosphate and dicyclohexyl-carbodiimide in pyridine followed by cation exchange chromatographic procedures was found to provide an efficient mute to a new series (3b-3d) of promising 3,4-O-cyclic phosphate prodrugs designated phenpanstatin phosphates. Application of analogous reaction conditions to pancratistatin (1a) led to a mixture of monophosphate derivatives where sodium paancratistatin 4-O-phosphate (4a) was isolated and the structure confirmed by x-ray craxtallography. Modification of the reaction conditions allowed direct phosphorylation of pancratistatin followed by cation exchange chromatography to afford sodium pancratistatin 3,4-O-cyclic phosphate (5b) which was selected for preclinical development.

Abstract: A process for preparing alendronate sodium includes the reaction of gammabutyric acid with phosphorous acid and phosphorus trichioride and subsequent treatment with an aqueous solution of an alkali metal hydroxide, in which the reaction is conducted in liquid ionic solvents.

Abstract: Novel FBPase inhibitors of the formula I and X are useful in the treatment of diabetes and other conditions associated with elevated blood glucose.

Abstract: Fluorescent labeled reporter compounds having a modified cyanine dye that is coupled to a nucleotide derivative through a linker are disclosed. The compounds are useful for nucleic acid sequence analysis. The fluorescent labeled reporter compounds are ring-locked cyanine dyes that are coupled to a nucleotide derivative, such as a modified DNA base, through a linker. These fluorescent labeled reporter compounds can be used as DNA chain-terminators in DNA synthesis to generate DNA fragments that are fluorescently-labeled at the 3?-terminal end of the DNA fragment.

Abstract: Tricyclic compounds according to the structure below, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed. A1 and A2 are moieties forming a five, six, or seven membered ring. L is a bond or a linker connecting a ring atom of Ar to N. X is O, S, or substituted nitrogen. Ar is aryl or heteroaryl. Q is N, +NR, or CR4. The aryl carbons may be independently substituted with substituents other than hydrogen. The compounds may include prodrug moieties covalently attached at any site.

Abstract: Novel compounds comprising a C—C double bond substituted at one carbon with two sulfur atom-containing groups are disclosed. The compounds are useful in methods and compositions for generating chemiluminescence rapidly by reaction with a peroxidase enzyme and a peroxide. The chemiluminescence thus produced can be used as a detectable signal in assays for peroxidase enzymes or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs.

Abstract: Disclosed are compounds of general formula (I) that function as prodrugs, thereby increasing bioavailabilities of the linked therapeutic agents, wherein the LINKER is (i) substituted or unsubstituted alkyl, (ii) substituted or unsubstituted alkenyl, (iii) substituted or unsubstituted alkanoyl, (iv) substituted or unsubstituted alkenoyl wherein the double bond is cis, and (v) (ortho or para) carbonyl-substituted aryl; and wherein the subtituent is each an independent group or linked together thereby forming a ring; and wherein X is one or more substituted or unsubstituted group containing one or more O, N, or S atom and wherein the substituent is each an independent group or linked together thereby forming a ring; and wherein the therapeutic agent is an alcohol-containing water-insoluble steroids or another alcohol containing compounds and methods to prepare such compounds.

Abstract: The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel ?-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic ?-lactamase inhibitors presently available, and which do not require a ?-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.

Abstract: The invention relates to compounds of the general formula (and pharmaceutically acceptable derivatives thereof): in which RA, RB, RC, RD, R5, R7, R9, R9a, AK, p, q, r and X are as defined herein, and to their preparation and use.

Abstract: This invention relates to compounds of the general formula: in which RA, RB, RC and RD are as defined herein, and to their preparation and use.

Abstract: The invention pertains to fused cyclic compounds having the formula, wherein G is an optionally substituted aryl or heterocyclo, L is an optional linker, M is a bond, O, CR7R7? or NR10, and M? is a bond or NR10, with the proviso that at least one of M or M? must be a bond; E is C?Z2, CR7CR7?, SO2, P?OR2, or P?OOR2; Z1 is O, S, NH, or NR6; Z2 is O, S, NH, or NR6; A1 is CR7 or N; A2 is CR7 or N; Y is J—J?—J? where J is (CR7R7?)n and n=0-3, J? is a bond or O, S, S?O, SO2, NH, NR6, C?O, OC?O, NR1C?O, CR7R7?, C?CR8R8?, R2P?O, OPOOR2, OPO2, OSO2, C?N, NHNH, NHNR6, NR6NH, N?N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo or aryl or substituted aryl, and J? is (CR7R7?)n and n=0-3; W is CR7R7?—CR7R7?, CR8?CR8?, CR7R7?—C?O, NR9—CR7R7?, N?CR8, N?N, NR9—NR9?, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl; and O, R2, R6, R7, R7?, R8, R8?, R9, R9

Abstract: The invention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel ?-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic ?-lactamase inhibitors presently available, and which do not require a ?-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.

Abstract: An isoquinuclidine derivative represented by the following general formula (I): (I) [wherein A1 is methylene or carbonyl]: R1 is hydrogen or methyl: R2 is —(CH2)n-A2-Ph (n is an integer of 0 to 3 and A2 is a single bond or —O—): and R3 is —COOH, —COOR4, —COSR4 (R4 is lower alkyl, unsubstituted phenyl, or phenyl substituted by a lower alkyl, lower alkoxy, hydroxyl, methoxycarbonyl, ethoxycarbonyl, or trifluoromethanesulfonamide group or by a halogen atom), etc.] or a pharmaceutically acceptable salt of the compound. Also provided is an oral remedy for diabetes, which contains the compound and has hypoglycemic activity.

Abstract: The present invention relates to an improved and economical process for the isolation of anticancer agent Camptothecin from the twigs and stem of Nothapodytes foetida using hot extraction 20(S) Camptothecin is an alkaloid, which contains a pentacyclic ring system that includes a pyrrolo [3,4-b] quinoline moiety (ring A, B and C), the pyridone ring D and a chiral center at C-20 in ring E.

Abstract: The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel ?-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic ?-lactamase inhibitors presently available, and which do not require a ?-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.

Abstract: Novel compounds comprising a C—C double bond substituted at one carbon with two sulfur atom-containing groups are disclosed. The compounds are useful in methods and compositions for generating chemiluminescence rapidly by reaction with a peroxidase enzyme and a peroxide. The chemiluminescence thus produced can be used as a detectable signal in assays for peroxidase enzymes or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs.

Abstract: The present invention provides for pyridoxine phosphonate analogues such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)alkylphosphonates, and (2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridyl)azaalkylphosphonates) and to pyridoxine malonate analogues, such as, for example, ((2-methyl-3-hydroxy-4-hydroxymethyl-5-pyridylmethyl)malonates), pharmaceutical compositions, and methods for treatment of cardiovascular and related diseases, and diabetes mellitus and related diseases.

Abstract: Novel compounds comprising a C—C double bond substituted at one carbon with two sulfur atom-containing groups are disclosed. The compounds are useful in methods and compositions for generating chemiluminescence rapidly by reaction with a peroxidase enzyme and a peroxide. The chemiluminescence thus produced can be used as a detectable signal in assays for peroxidase enzymes or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs.

Abstract: Novel pyridinones and their derivatives which are effective in treating or preventing Gram-negative bacterial infections are provided. The pyridinones are stable and easily derivatized; the methods by which these derivatizations occur is described. Two regioselective and functional group tolerant methods for the synthesis of the novel pyridinones are also provided. One such synthetic method involves reacting an imine and a Meldrum's acid derivative in solution. The other synthetic method is a solid phase synthesis of the pyridinones in which an imine is prepared bound to a solid support and a Meldrum's acid derivative is reacted with the imine. Novel imine intermediates useful in the solid phase and solution methods of synthesizing the pyridionones are also described.

Abstract: Aminoisoquinoline derivatives of the following formulae or analogs thereof and pharmaceutically acceptable salts thereof are provided. These compounds have an excellent effect of inhibiting activated blood-coagulation factor X, and they are useful as anticoagulants or agents for preventing or treating thrombi or emboli.

Abstract: Chiral ligands and metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The metal complexes according to the present invention are useful as catalysts in asymmetric reactions, such as, hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; epoxidation, kinetic resolution and [m+n] cycloaddition. Processes for the preparation of the ligands are also described.

Abstract: Compounds of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, A, D, X, Y and Z have the meaning as defined in the claims, exhibit protein tyrosine kinase and protein serin/threonine kinase inhibitory activity.

Abstract: Compounds of the following structure are HMG CoA reductase inhibitors and thus are active in inhibiting cholesterol biosynthesis, modulating blood serum lipids such as lowering LDL cholesterol and/or increasing HDl cholesterol, and treating hyperlipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis and pharmaceutically acceptable salts thereof, wherein X is O, S, SO, SO2 or NR7; Z is n is 0 or 1; R1 and R2 are the same or different and are independently selected from alkyl, arylalkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, heteroaryl or cycloheteroalkyl; and R3 to R10 are as defined herein.

Abstract: The present invention includes novel retinoid compounds that have selectivity as RXR agonists on one or more isoforms of RXR, currently, RXR&agr;, RXR&bgr;, or RXR&ggr;. The present compounds, and pharmaceutical compositions incorporating these compounds, therefore, are effective in treating conditions mediated by RXRs. Among other physiological responses, the compounds of the present invention reduce blood glucose and maintain body weight, and, thus, are useful for the treatment of diabetes (NIDDIM) and obesity.

Abstract: Novel compounds comprising a C—C double bond substituted at one carbon with two sulfur atom-containing groups are disclosed. The compounds are useful in methods and compositions for generating chemiluminescence rapidly by reaction with a peroxidase enzyme and a peroxide. The chemiluminescence thus produced can be used as a detectable signal in assays for peroxidase enzymes or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs.

Abstract: The invention relates to compounds of the general formula (and pharmaceutically acceptable derivatives thereof): 1

Abstract: This invention relates to compounds of the general formula: 1

Abstract: The present invention relates to inhibitors of p38, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: The present invention is directed to phosphonic acid compounds useful as serine protease inhibitors, compositions thereof and methods for treating inflammatory and serine protease mediated disorders.

Abstract: New ligands, compositions, metal-ligand complexes and arrays with pyridyl-amine ligands are disclosed that catalyze the polymerization of monomers into polymers. Certain of these catalysts with hafnium metal centers have high performance characteristics, including higher comonomer incorporation into ethylene/olefin copolymers, where such olefins are for example, 1-octene, isobutylene or styrene. Certain of the catalysts are particularly effective at polymerizing propylene to high molecular weight isotactic polypropylene in a solution process at a variety of polymerization conditions.

Abstract: The present invention relates to novel chiral phosphorus compounds which can be readily prepared from quinoline derivatives as inexpensive starting compounds and have the general formula I wherein R1, R2, R3, R4, R5 are chiral or achiral organic residues which are derived from substituted or unsubstituted straight or branched chain or cyclic aliphatic or aromatic groups and which, in the case of the pairs R1/R2 and R4/R5, may be interconnected. Further, the invention relates to the use of chiral phosphorus compounds of general formula I as catalysts or catalyst components in processes for the preparation of optically active products.

Abstract: An isoquinuclidine derivative represented by the following general formula (I): (I) [wherein A1 is methylene or carbonyl]: R1 is hydrogen or methyl: R2 is —(CH2)n-A2-Ph (n is an integer of 0 to 3 and A2 is a single bond or —O—): and R3 is —COOH, —COOR4, —COSR4 (R4 is lower alkyl, unsubstituted phenyl, or phenyl substituted by a lower alkyl, lower alkoxy, hydroxyl, methoxycarbonyl, ethoxycarbonyl, or trifluoromethanesulfonamide group or by a halogen atom), etc.] or a pharmaceutically acceptable salt of the compound. Also provided is an oral remedy for diabetes, which contains the compound and has hypoglycemic activity.

Abstract: The invention relates to compounds of the general formula (and pharmaceutically acceptable derivatives thereof): in which RA, RB, RC, RD, R5, R7, R9, R9a, AK, p, q, r and X are as defined herein, and to their preparation and use.

Abstract: The intention relates to bacterial antibiotic resistance and, in particular, to compositions and methods for overcoming bacterial antibiotic resistance. The invention provides novel &bgr;-lactamase inhibitors, which are structurally unrelated to the natural product and semi-synthetic &bgr;-lactamase inhibitors presently available, and which do not require a &bgr;-lactam pharmacophore. The invention also provides pharmaceutical compositions and methods for inhibiting bacterial growth.